21-33287341-G-GGTTT

Variant names:

• chr21-33287341-G-GGTTT
• rs1610997
• NM_000628.5:c.647-754_647-751dupGTTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000628.5(IL10RB):​c.647-754_647-751dupGTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.51 (20561 hom., cov: 0)
• Consequence: IL10RB NM_000628.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.244
• Publications: 2 publications found

Genes affected

IL10RB (HGNC:5965): (interleukin 10 receptor subunit beta) The protein encoded by this gene belongs to the cytokine receptor family. It is an accessory chain essential for the active interleukin 10 receptor complex. Coexpression of this and IL10RA proteins has been shown to be required for IL10-induced signal transduction. This gene and three other interferon receptor genes, IFAR2, IFNAR1, and IFNGR2, form a class II cytokine receptor gene cluster located in a small region on chromosome 21. [provided by RefSeq, Jul 2008]

IL10RB Gene-Disease associations (from GenCC):

• inflammatory bowel disease 25

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• IL10-related early-onset inflammatory bowel disease

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFNAR2-IL10RB (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000628.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	NM_000628.5	MANE Select	c.647-754_647-751dupGTTT		intron	N/A	NP_000619.3
	IFNAR2-IL10RB	NM_001414505.1		c.1307-754_1307-751dupGTTT		intron	N/A	NP_001401434.1	H0Y3Z8
	IL10RB	NM_001405850.1		c.647-754_647-751dupGTTT		intron	N/A	NP_001392779.1	A0A1B0GU52

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IL10RB	ENST00000290200.7	TSL:1 MANE Select	c.647-763_647-762insGTTT		intron	N/A	ENSP00000290200.2	Q08334
	IFNAR2-IL10RB	ENST00000433395.7	TSL:5	c.1307-763_1307-762insGTTT		intron	N/A	ENSP00000388223.3	H0Y3Z8
	IL10RB	ENST00000896213.1		c.641-763_641-762insGTTT		intron	N/A	ENSP00000566272.1

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76458 AN: 150756 Hom.: 20525 Cov.: 0

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.436

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.488

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.507 AC: 76533 AN: 150872 Hom.: 20561 Cov.: 0 AF XY: 0.502 AC XY: 37028 AN XY: 73710

African (AFR) AF: 0.693 AC: 28378 AN: 40922

American (AMR) AF: 0.407 AC: 6191 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1931 AN: 3462

East Asian (EAS) AF: 0.207 AC: 1061 AN: 5138

South Asian (SAS) AF: 0.374 AC: 1784 AN: 4776

European-Finnish (FIN) AF: 0.469 AC: 4871 AN: 10382

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.454 AC: 30739 AN: 67694

Other (OTH) AF: 0.482 AC: 1014 AN: 2102

Alfa AF: 0.305 Hom.: 606

Asia WGS AF: 0.273 AC: 950 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.24
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1610997; hg19: chr21-34659646;